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Authors & Affiliations
Taichi Hiraga, Toshiaki Hata, Shingo Soya, Joshua Johansen, Tomonori Takeuchi, Masahiro Okamoto, Hideaki Soya
Abstract
Physical exercise benefits the dorsal hippocampus (dHPC) and promotes learning and memory. We have focused on light exercise (LEX) and have revealed that this accessible form of exercise can effectively increase hippocampal activity and enhance memory performance. However, the circuit mechanism underlying this benefit remains largely undetermined. Our recent findings demonstrate that LEX can stimulate tyrosine hydroxylase-positive (TH+) neurons in the locus coeruleus (LC) and the ventral tegmental area (VTA), and increase noradrenaline (NA) and dopamine (DA) release in the dHPC. This raises the question that DAergic and/or NAergic projections to the dHPC contribute to the LEX’s benefit to memory enhancement. To examine this hypothesis, we employed a rat treadmill exercise model combined with an object location task (OLT) and confirmed that post-encoding-LEX enhanced memory retention over 24 hours in a dorsal hippocampal D1/D5 receptor-dependent but β-adrenergic receptor-independent manner. Further investigation through anterograde tracing showed that LC-TH+ neurons project more densely than VTA-TH+ neurons to the dHPC. Besides, the retrograde tracing study indicated that LEX activated dHPC-projecting TH+ neurons at the LC, but not the VTA. Subsequently, we revealed that chemogenetic activation of LC-TH+ neurons increased DA release in the dHPC and mimicked LEX-enhanced OLT memory retention. Conversely, chemogenetic inhibition of LC-TH+ neurons diminished DA release in the dHPC and LEX-induced memory enhancement in OLT. Overall, our findings unveil a pivotal role for the coeruleo-hippocampal DAergic pathway in LEX-induced memory consolidation. This research illuminates the circuit mechanisms of exercise-enhanced memory and opens avenues for LEX-based accessible memory-enhancement strategies.